4-hydroxy[1,5]naphthyridine-3-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】43932

【品名】4-hydroxy[1,5]naphthyridine-3-carboxylic acid

【CA登记号】

【分子式】C₉H₆N₂O₃

【分子量】190.15832

【元素组成】C 56.85% H 3.18% N 14.73% O 25.24%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

The known 4-hydroxy-1,5-naphthyridine-3-carboxylic acid (I) was decarboxylated to (II) upon refluxing in quinoline. Heating of (II) with POCl3 furnished 4-chloro-1,5-naphthyridine (III), which was converted to amine (IV) by reaction with n-propylamine in pyridine. Curtius rearrangement of 2-methyl-6-benzoxazolecarboxylic acid (V) in the presence of diphenylphosphoryl azide gave isocyanate (VI). Finally, coupling between isocyanate (VI) and amine (IV) provided the title urea.

参考文献中间体

合成目标

【1】 Johns, A.; Porter, R.A. (SmithKline Beecham plc); Phenylurea and phenylthio urea derivs.. EP 1075478; WO 9958533 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	43932	4-hydroxy[1,5]naphthyridine-3-carboxylic acid	C₉H₆N₂O₃	详情	详情
(II)	43933	[1,5]naphthyridin-4-ol	C₈H₆N₂O	详情	详情
(III)	43934	4-chloro[1,5]naphthyridine	C₈H₅ClN₂	详情	详情
(IV)	43935	[1,5]naphthyridin-4-amine; [1,5]naphthyridin-4-ylamine	C₈H₇N₃	详情	详情
(V)	43936	2-methyl-1,3-benzoxazole-6-carboxylic acid	C₉H₇NO₃	详情	详情
(VI)	43937	6-isocyanato-2-methyl-1,3-benzoxazole; 2-methyl-1,3-benzoxazol-6-yl isocyanate	C₉H₆N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The cyclization of 3aminopyridine (I) with diethyl ethoxymethylenemalonate (II) in refluxing Dowtherm gives 4-hydroxy-1,5-naphthyridine-3-carboxylic acid ethyl ester (III), which is hydrolyzed with NaOH in refluxing water to yield the corresponding hydroxyacid (IV). The decarboxylation of (IV) by heating at 320 C in mineral oil affords 4-hydroxy-1,5-naphthyridine (V), which is acylated with trifluoromethanesulfonic anhydride to provide the triflate (VI). The reaction of (VI) with propylamine in pyridine affords 4-amino-1,5-naphthyridine (VII), which is condensed with 2-methylbenzoxazole-6-ylcarbonyl azide (VIII) (obtained by reaction of the corresponding acid (IX) with DPPA) in refluxing toluene to provide the target urea.

参考文献中间体

合成目标

【1】 Porter, R.A.; et al.; 1,3-Biarylureas as selective non-peptide antagonists of the orexin-1 receptor. Bioorg Med Chem Lett 2001, 11, 14, 1907.
【2】 Adams, J.T.; et al.; Synthesis of antimalarials. VI. Synthesis of certain 1,5- and 1,8-naphthyridine derivatives. J Am Chem Soc 1946, 68, 1317.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	33327	3-Pyridinylamine; 3-Aminopyridine; 3-Pyridinamine	462-08-8	C₅H₆N₂	详情	详情
(II)	14088	Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate	87-13-8	C₁₀H₁₆O₅	详情	详情
(III)	53616	ethyl 4-hydroxy[1,5]naphthyridine-3-carboxylate	13801-51-9	C₁₁H₁₀N₂O₃	详情	详情
(IV)	43932	4-hydroxy[1,5]naphthyridine-3-carboxylic acid		C₉H₆N₂O₃	详情	详情
(V)	43933	[1,5]naphthyridin-4-ol		C₈H₆N₂O	详情	详情
(VI)	53617	[1,5]naphthyridin-4-yl trifluoromethanesulfonate	n/a	C₉H₅F₃N₂O₃S	详情	详情
(VII)	43935	[1,5]naphthyridin-4-amine; [1,5]naphthyridin-4-ylamine		C₈H₇N₃	详情	详情
(VIII)	53618	2-methyl-1,3-benzoxazole-6-carbonyl azide	n/a	C₉H₆N₄O₂	详情	详情
(IX)	43936	2-methyl-1,3-benzoxazole-6-carboxylic acid		C₉H₇NO₃	详情	详情

Extended Information